This project involves work in three areas, gallstone dissolution and growth, transport processes in bile, and dynamics of micelle exchange. Progress in the first area has been considerable. We have completed studies of the rate controlling steps of gallstone dissolution, and have defined the regions in which gallstone dissolution can be easily accelerated. We are now generalizing these results so that they can be applied to solubilization in the small intestine. During the next year, we also plan to finish measurements of initial gallstone growth. Because our apparatus for these studies is so sensitive, we now know that there is no "metastable region" or "lag time" in cholesterol precipitation. We have also largely completed our studies of the second area, transport processes in bile. Diffusion measurements show that bile salt diffuses by a radically different mechanism than lecithin and cholesterol; this difference in mechanism may affect gallstone growth rates. The chief remaining effort in this area is to complete studies of electrophoresis, which allows a complete determination of the charge on the bile salt micelle. Work in the third area, the dynamics of micelle exchange, we postponed becaused actual funding was less than the total authorized. We will start work in this area during the next year, initially emphasizing rapid exchange rates between micelles. Fast reaction studies like this one will then be combined with transport properties in bile to further elucidate the mechanisms responsible for gallstone growth and dissolution. This integrated approach coupling three research areas will increase the value of the work.